Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties.

Abstract

We have tested the hypothesis that oxidation of lung surfactant results in loss ofsurface tension lowering function. Porcine lung surfactant was exposed to conditions known to cause lipid peroxidation (0.2 mM FeCl2 + 0.1 mM H202 or 5 ,uM CuC12). Lipid peroxidation was verified by detection of conjugated dienes, thiobarbituric acid reactive substances, fluorescent products, hydroxy alkenals, and loss of unsaturated fatty acids. Exposed samples had significantly diminished surface tension lowering ability in vitro as measured in a bubble surfactometer. Samples exposed to FeCl2 + H202 had significantly diminished surface tension lowering ability in vivo as indicated by their reduced ability to improve lung compliance of surfactant-deficient fetal rabbits. Oxidation of phospholipid mixtures with surface tension lowering activity and containing unsaturated acyl groups resulted in partial loss of activity as determined in vitro. These results suggest that the effect of oxidants on lung surfactant function is due, in part, to effects on the phospholipid components and that acute pulmonary inflammation accompanied by oxygen radical production may result in surfactant lipid peroxidation and loss of surface tension lowering function. (J. Clin. Invest. 1994. 93:2608-2615

Lung Surfactant Gelation Induced by Epithelial Cells Exposed to Air Pollution or Oxidative Stress

“…Air pollutants have also been recognized to influence the structure and function of the lung surfactant system (6,7). Oxidative inactivation of surfactant by cellular reactive oxygen species (ROS), leading to surfactant lipid peroxidation, protein carbonylation, and functional impairment of surfactant protein A, are thought to be possible mechanisms underlying air pollutantinduced surfactant damage (7)(8)(9)(10)(11). Oxidative damage to lung epithelial cells is a component of acute lung injury and associated respiratory failure (12).…”

Exogenous surfactant in acute respiratory distress syndrome: more is better

“…This loss of alveolar surfactant is due to several factors including the presence of plasma proteins [13], cleavage of phospholipids by serum phospholipases [14], formation of free radical species (including nitrates, lipid peroxidation, etc.) [15][16][17], and conversion to nonfunctional surfactant with more phospholipid aggregates [14].…”

“…Exosurf1 is an exogenous surfactant that does not contain apoproteins and this can affect the onset of action and be inhibited by serum proteins. The study by GREGORY et al [19] used a bovine surfactant that contains two apoprotein constituents, whereas the synthetic preparation contains neither protein nor peptides and needs to achieve an in vitro critical concentration in order to exert its effects [16]. These data suggest that for an exogenous surfactant preparation to be effective, it must contain apoproteins.…”

Inhibitory effect of porcine surfactant on the respiratory burst oxidase in human neutrophils. Attenuation of p47phox and p67phox membrane translocation as the mechanism.

“…One hallmark of ARDS is the intense inflammation detected in the lung as evidenced by the dramatic increase in the number of PMN that are present in histologic sections or recovered in lavage fluid from patients (7). The release of neutrophil-derived proteases and reactive oxygen intermediates (ROI) has also been implicated in disease pathogenesis, and a number of observations have suggested that these inflammatory products may modify structure or function of lung surfactant (8,9).…”